This report covers three projects which are currently in progress. The major project is a study of the origin, mode of action, and metabolism of Gamma-hydroxybutyrate (GHB). Biological factors which regulate the enzyme that converts GHB to succinic semialdehyde (SSA) have been determined. An antibody to this enzyme is being used to establish its identity with D-glucuronate reductase. Several compounds such as putrescine, arginine, and Beta-hydroxybutyrate have been shown to increase GHB levels. Present studies are directed toward determining the preferred precursor. A second area of study concerns the effect of elevated levels of acetoacetate on the formation of GTP. A good inverse correlation between blood acetoacetate and brain cyclic GMP has been established and suggests that GTP synthesis may be decreased in the mitochondria in disease states such as diabetes in which severe ketosis can occur. Experiments are in progress to measure the effect of ketosis on mitochondrial GTP formation in the brain. A third project nearing completion has demonstrated that 2-deoxy-D-glucose can be incorporated into glycogen. Measurements of the amount of 2-deoxy-D-glucose which is incorporated into brain glycogen in 45 minutes indicates that it comprises 1-2 percent of the radioactive material in brain.